Fig. 1: Overview of multi-tissue TWAS, colocalization, and MR-based gene prioritisation for colorectal cancer risk.
a Flowchart showing analysis overview and number of genes/splicing events identified at each stage. “Genes with robust evidence” includes those that had H4 above 0.8 in colocalisation analyses, and which either passed Bonferroni correction in the relevant MR analysis (p < 4.38 × 10−5; 0.05/N*G where N is the number of gene-tissue pairs (161) and G is the number of CRC GWAS (7) for genes identified in TWAS analyses or p < 1.32 × 10−4; 0.05/number of druggable genes with suitable genetic instruments available (380) for genes identified as part of the druggable genome) or which did not have suitable instruments available to be included in the MR analysis. MR Mendelian randomisation. b Manhattan plot showing results of S-MultiXcan and JTI TWAS analyses of colorectal cancer risk, for all anatomical subsites combined. Where genes were identified in multiple TWAS analyses, the one with the lowest p value was retained. Genes labelled are those prioritised following subsequent analyses. All statistical tests were two-sided with the unadjusted p values from S-MultiXcan or JTI plotted. c Venn diagram showing overlap of final prioritised 37 genes identified by each TWAS analysis. JTI joint tissue imputation, eQTLs expression quantitative trait loci, sQTLs splice quantitative trait loci. Source data are provided as a Source Data file.
